Our working hypothesis is that mammalian cellular responses are changed by filarial-derived factors that may circulate, and that these alterations contribute to the pathogenesis of filarial diseases. Specifically, we are interested in the hypothesis that endothelium-mediated regulation of vascular and lymphatic smooth muscle is altered, in vivo and in vitro, by biologically active factors released by filarial nematodes, and we believe that filarial-induced changes in mammalian cell behavior are responsible, in part, for the vascular and lymphatic dysfunction that characterize human and animal filariasis. We have continued to use a variety of techniques to identify filarial factors and then assess their biological activity in vitro. This tedious approach is the only way we know of to determine what the parasites make and what role these factors may playin the pathogenesis of filariasis. Worldwide, over 400,000,000 people and countless animals are infected with filarial parasites. Circulating filarial factors have the potential to interact with any mammalian cell, and parasite-induced alteration in cellular metabolism and function could play an important role in the pathogenesis of human and animal filariasis. Thus, pharmacologic intervention aimed at altering parasite metabolism, rather than at eradicating the parasites or the vector, could, in this complicated scenario, prove beneficial.